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Published 10 April 2006. doi:10.1083/jcb.200506159
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 173, Number 1, 69-82
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Article

 Drosophila melanogaster Scramblases modulate synaptic transmission

Usha Acharya1,2, Michael Beth Edwards1, Ramon A. Jorquera3,5, Hugo Silva3, Kunio Nagashima4, Pedro Labarca3, and Jairaj K. Acharya1

1 Laboratory of Protein Dynamics and Signaling, National Cancer Institute Frederick, Frederick, MD 21702
2 Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605
3 Centro de Estudios Científicos, Valdivia 511-0246, Chile
4 EM Facility/Image Analysis Laboratory, Science Applications International Corporation Frederick, Frederick, MD 21702
5 Universidad Austral de Chile, Valdivia 509-9200, Chile

Correspondence to Jairaj K. Acharya: acharyaj{at}mail.ncifcrf.gov

Scramblases are a family of single-pass plasma membrane proteins, identified by their purported ability to scramble phospholipids across the two layers of plasma membrane isolated from platelets and red blood cells. However, their true in vivo role has yet to be elucidated. We report the generation and isolation of null mutants of two Scramblases identified in Drosophila melanogaster. We demonstrate that flies lacking either or both of these Scramblases are not compromised in vivo in processes requiring scrambling of phospholipids. Instead, we show that D. melanogaster lacking both Scramblases have more vesicles and display enhanced recruitment from a reserve pool of vesicles and increased neurotransmitter secretion at the larval neuromuscular synapses. These defects are corrected by the introduction of a genomic copy of the Scramb 1 gene. The lack of phenotypes related to failure of scrambling and the neurophysiological analysis lead us to propose that Scramblases play a modulatory role in the process of neurotransmission.

M.B. Edwards, R. Jorquera, and H. Silva contributed equally to this paper.

Abbreviations used in this paper: dsRNA, double-stranded RNA; ECP, exo/endo pool of SVs; EMS, ethyl methane sulfonate; GMR, glass multimer reporter; NMJ, neuromuscular junction; PS, phosphatidylserine; PTP, posttetanic potentiation; RP, reserve pool; S2 cells, Schneider cells; SV, synaptic vesicle; UAS, upstream activating sequence.


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